title: Reactive oxygen species exacerbate autoimmune hemolytic anemia in New Zealand Black mice.
abstract: Elevated reactive oxygen species (ROS) and oxidative damage occur in the red blood cells (RBCs) of SOD1-deficient C57BL/6 mice. This leads to autoimmune responses against RBCs in aged mice that are similar to autoimmune hemolytic anemia (AIHA). We examined whether a SOD1 deficiency and/or the human SOD1 transgene (hSOD1) would affect phenotypes of AIHA-prone New Zealand Black (NZB) mice by establishing three congenic strains: those lacking SOD1, those expressing hSOD1 under a GATA-1 promoter, and those lacking mouse SOD1 but expressing hSOD1. Levels of intracellular ROS and oxidative stress markers increased, and the severity of the AIHA phenotype was aggravated by a SOD1 deficiency. In contrast, the transgenic expression of hSOD1 in an erythroid cell-specific manner averted most of the AIHA phenotype evident in the SOD1-deficient mice and also ameliorated the AIHA phenotype in the mice possessing intrinsic SOD1. These data suggest that oxidative stress in RBCs may be an underlying mechanism for autoimmune responses in NZB mice. These results were consistent with the hypothetical role of reactive oxygen species in triggering the autoimmune reaction in RBCs and may provide a novel approach to mitigating the progression of AIHA by reducing oxidative stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Konno
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuki
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kibe
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Iuchi
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan. Electronic address: jfujii@med.id.yamagata-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D004912:Erythrocytes / Q000201:enzymology* / Q000276:immunology; D050982:GATA1 Transcription Factor / Q000235:genetics; D008136:Longevity; D008706:Methemoglobin / Q000032:analysis; D051379:Mice; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D054464:Peroxiredoxins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017382:Reactive Oxygen Species / Q000276:immunology*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D001323:Autoantibodies; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D008706:Methemoglobin; D054464:Peroxiredoxins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Autoimmune hemolytic anemia; Free radicals; NZB mouse; Red blood cells; SOD1